(-)-17-Cyclopropylmethyl-3,14beta-dihydroxy-4,5alpha-epoxy-6beta-[N-methyl-3-trans-3-(3-furyl) acrylamido]
morphinan hydrochloride (TRK-820) is a
kappa-opioid receptor agonist that has pharmacological characteristics different from typical
kappa-opioid receptor agonists. This study was conducted to determine the antiallodynic and antihyperalgesic effects of
TRK-820 in a mouse model of acute herpetic
pain and to compare them with those of the
kappa-opioid receptor agonist
enadoline and the
mu-opioid receptor agonist
morphine. Percutaneous inoculation with herpes simplex virus type-1 induced
tactile allodynia and
mechanical hyperalgesia in the hind paw on the inoculated side.
TRK-820 (0.01-0.1 mg/kg p.o.),
enadoline (1-10 mg/kg p.o.) and
morphine (5-20 mg/kg p.o.) dose dependently inhibited the
allodynia and
hyperalgesia, but the antiallodynic and antihyperalgesic dose of
enadoline markedly decreased spontaneous locomotor activity. The antinociceptive action of
TRK-820 (0.1 mg/kg) was completely antagonized by pretreatment with
norbinaltorphimine, a
kappa-opioid receptor antagonist, but not by
naltrexone, a
mu-opioid receptor antagonist. Repeated treatment with
morphine (20 mg/kg, four times) resulted in the reduction of antiallodynic and antihyperalgesic effects, whereas the inhibitory potency of
TRK-820 (0.1 mg/kg) was almost the same even after the fourth administration. There was no cross-tolerance in antinociceptive activities between
TRK-820 and
morphine. Intrathecal and intracerebroventricular, but not intraplantar,
injections of
TRK-820 (10-100 ng/site) suppressed the
allodynia and
hyperalgesia. These results suggest that
TRK-820 inhibits acute herpetic
pain through
kappa-opioid receptors in the spinal and supraspinal levels.
TRK-820 may have clinical efficacy in acute herpetic
pain with enough safety margins.